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Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells

For multiple sclerosis, genome wide association studies and follow up studies have identified susceptibility single nucleotide polymorphisms located in or near CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1 in addition to CLEC16A. These genetic variants are located i...

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Autores principales: Leikfoss, Ingvild S., Keshari, Pankaj K., Gustavsen, Marte W., Bjølgerud, Anja, Brorson, Ina S., Celius, Elisabeth G., Spurkland, Anne, Bos, Steffan D., Harbo, Hanne F., Berge, Tone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512731/
https://www.ncbi.nlm.nih.gov/pubmed/26203907
http://dx.doi.org/10.1371/journal.pone.0132957
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author Leikfoss, Ingvild S.
Keshari, Pankaj K.
Gustavsen, Marte W.
Bjølgerud, Anja
Brorson, Ina S.
Celius, Elisabeth G.
Spurkland, Anne
Bos, Steffan D.
Harbo, Hanne F.
Berge, Tone
author_facet Leikfoss, Ingvild S.
Keshari, Pankaj K.
Gustavsen, Marte W.
Bjølgerud, Anja
Brorson, Ina S.
Celius, Elisabeth G.
Spurkland, Anne
Bos, Steffan D.
Harbo, Hanne F.
Berge, Tone
author_sort Leikfoss, Ingvild S.
collection PubMed
description For multiple sclerosis, genome wide association studies and follow up studies have identified susceptibility single nucleotide polymorphisms located in or near CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1 in addition to CLEC16A. These genetic variants are located in intronic or intergenic regions and display strong linkage disequilibrium with each other, complicating the understanding of their functional contribution and the identification of the direct causal variant(s). Previous studies have shown that multiple sclerosis-associated risk variants in CLEC16A act as expression quantitative trait loci for CLEC16A itself in human pancreatic β-cells, for DEXI and SOCS1 in thymic tissue samples, and for DEXI in monocytes and lymphoblastoid cell lines. Since T cells are major players in multiple sclerosis pathogenesis, we have performed expression analyses of the CIITA-DEXI-CLEC16A-SOCS1 gene cluster in CD4+ and CD8+ T cells isolated from multiple sclerosis patients and healthy controls. We observed a higher expression of SOCS1 and CLEC16A in CD4+ T cells in samples homozygous for the risk allele of CLEC16A rs12927355. Pair-wise linear regression analysis revealed high correlation in gene expression in peripheral T cells of CIITA, DEXI, CLEC16A and SOCS1. Our data imply a possible regulatory role for the multiple sclerosis-associated rs12927355 in CLEC16A.
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spelling pubmed-45127312015-07-24 Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells Leikfoss, Ingvild S. Keshari, Pankaj K. Gustavsen, Marte W. Bjølgerud, Anja Brorson, Ina S. Celius, Elisabeth G. Spurkland, Anne Bos, Steffan D. Harbo, Hanne F. Berge, Tone PLoS One Research Article For multiple sclerosis, genome wide association studies and follow up studies have identified susceptibility single nucleotide polymorphisms located in or near CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1 in addition to CLEC16A. These genetic variants are located in intronic or intergenic regions and display strong linkage disequilibrium with each other, complicating the understanding of their functional contribution and the identification of the direct causal variant(s). Previous studies have shown that multiple sclerosis-associated risk variants in CLEC16A act as expression quantitative trait loci for CLEC16A itself in human pancreatic β-cells, for DEXI and SOCS1 in thymic tissue samples, and for DEXI in monocytes and lymphoblastoid cell lines. Since T cells are major players in multiple sclerosis pathogenesis, we have performed expression analyses of the CIITA-DEXI-CLEC16A-SOCS1 gene cluster in CD4+ and CD8+ T cells isolated from multiple sclerosis patients and healthy controls. We observed a higher expression of SOCS1 and CLEC16A in CD4+ T cells in samples homozygous for the risk allele of CLEC16A rs12927355. Pair-wise linear regression analysis revealed high correlation in gene expression in peripheral T cells of CIITA, DEXI, CLEC16A and SOCS1. Our data imply a possible regulatory role for the multiple sclerosis-associated rs12927355 in CLEC16A. Public Library of Science 2015-07-23 /pmc/articles/PMC4512731/ /pubmed/26203907 http://dx.doi.org/10.1371/journal.pone.0132957 Text en © 2015 Leikfoss et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Leikfoss, Ingvild S.
Keshari, Pankaj K.
Gustavsen, Marte W.
Bjølgerud, Anja
Brorson, Ina S.
Celius, Elisabeth G.
Spurkland, Anne
Bos, Steffan D.
Harbo, Hanne F.
Berge, Tone
Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells
title Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells
title_full Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells
title_fullStr Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells
title_full_unstemmed Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells
title_short Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells
title_sort multiple sclerosis risk allele in clec16a acts as an expression quantitative trait locus for clec16a and socs1 in cd4+ t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512731/
https://www.ncbi.nlm.nih.gov/pubmed/26203907
http://dx.doi.org/10.1371/journal.pone.0132957
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